Sex-specific alteration in human muscle transcriptome with age

Gharpure, Mohini; Chen, Jie; Nerella, Resheek; Vyavahare, Sagar; Kumar, Sandeep; Isales, Carlos M.; Hamrick, Mark W.; Adusumilli, Satish; Fulzele, Sadanand

doi:10.1007/s11357-023-00795-5

Cited by 5 publications

(1 citation statement)

References 52 publications

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“…While macrophages in the skeletal muscle microenvironment have been categorized, the specific subpopulations that are closely associated with the development of sarcopenia and their corresponding targets still require further investigation. Moreover, human muscle transcriptome exhibits sex-specific changes with aging ( 58 , 59 ). In addition, a correlation between the incidence of sarcopenia and age is observed as previously reported ( 5 , 60 ).…”

Section: Discussionmentioning

confidence: 99%

Characterizing the skeletal muscle immune microenvironment for sarcopenia: insights from transcriptome analysis and histological validation

Shen,

Zong,

Zhao

et al. 2024

Front. Immunol.

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BackgroundSarcopenia is a condition characterized by the age-related loss of skeletal muscle mass and function. The pathogenesis of the disease is influenced by chronic low-grade inflammation. However, the specific changes in the immune landscape changes of sarcopenic muscle are not yet fully understood.MethodsTo gain insights into the immune cell composition and interactions, we combined single-nucleus RNA sequencing data, bulk RNA sequencing dataset, and comprehensive bioinformatic analyses on the skeletal muscle samples from young, aged, and sarcopenic individuals. Histological staining was then performed on skeletal muscles to validate the distribution of immune cells in clinical samples.ResultsWe analyzed the transcriptomes of 101,862 single nuclei, revealing a total of 10 major cell types and 6 subclusters of immune cell types within the human skeletal muscle tissues. Notable variations were identified in the immune microenvironment between young and aged skeletal muscle. Among the immune cells from skeletal muscle microenvironment, macrophages constituted the largest fraction. A specific marker gene LYVE1 for skeletal muscle resident macrophages was further identified. Cellular subclasses included four distinct groups of resident macrophages, which play different roles in physiological or non-physiological conditions. Utilizing bulk RNA sequencing data, we observed a significant enrichment of macrophage-rich inflammation in sarcopenia.ConclusionsOur findings demonstrate age-related changes in the composition and cross-talk of immune cells in human skeletal muscle microenvironment, which contribute to chronic inflammation in aged or sarcopenia muscle. Furthermore, macrophages emerge as a potential therapeutic target, thus advancing our understanding of the pathogenesis of sarcopenia.

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Section: Discussionmentioning

confidence: 99%

Characterizing the skeletal muscle immune microenvironment for sarcopenia: insights from transcriptome analysis and histological validation

Shen,

Zong,

Zhao

et al. 2024

Front. Immunol.

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Physical activity intensity, frequency, duration, volume and the risk of possible sarcopenia in middle-aged and older adults

Zhao,

Zhang,

et al. 2023

GeroScience

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Sex dimorphism and tissue specificity of gene expression changes in aging mice

Zhu,

Arnold,

Samuelson

et al. 2024

Biol Sex Differ

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Background Aging is a complex process that involves all tissues in an organism and shows sex dimorphism. While transcriptional changes in aging have been well characterized, the majority of studies have focused on a single sex and sex differences in gene expression in aging are poorly understood. In this study, we explore sex dimorphism in gene expression in aging mice across three tissues. Methods We collected gastrocnemius muscle, liver and white adipose tissue from young (6 months, n = 14) and old (24 months, n = 14) female and male C57BL/6NIA mice and performed RNA-seq. To investigate sex dimorphism in aging, we considered two levels of comparisons: (a) differentially expressed genes between females and males in the old age group and (b) comparisons between females and males across the aging process. We utilized differential expression analysis and gene feature selection to investigate candidate genes. Gene set enrichment analysis was performed to identify candidate molecular pathways. Furthermore, we performed a co-expression network analysis and chose the gene module(s) associated with aging independent of sex or tissue-type. Results We identified both tissue-specific and tissue-independent genes associated with sex dimorphism in aged mice. Unique differentially expressed genes between old males and females across tissues were mainly enriched for pathways related to specific tissue function. We found similar results when exploring sex differences in the aging process, with the exception that in the liver genes enriched for lipid metabolism and digestive system were identified in both females and males. Combining enriched pathways across analyses, we identified amino acid metabolism, digestive system, and lipid metabolism as the core mechanisms of sex dimorphism in aging. Although the vast majority of age-related genes were sex and tissue specific, we identified 127 hub genes contributing to aging independent of sex and tissue that were enriched for the immune system and signal transduction. Conclusions There are clear sex differences in gene expression in aging across liver, muscle and white adipose. Core pathways, including amino acid metabolism, digestive system and lipid metabolism, contribute to sex differences in aging.

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Sex-specific alteration in human muscle transcriptome with age

Cited by 5 publications

References 52 publications

Characterizing the skeletal muscle immune microenvironment for sarcopenia: insights from transcriptome analysis and histological validation

Characterizing the skeletal muscle immune microenvironment for sarcopenia: insights from transcriptome analysis and histological validation

Physical activity intensity, frequency, duration, volume and the risk of possible sarcopenia in middle-aged and older adults

Sex dimorphism and tissue specificity of gene expression changes in aging mice

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